This project involves development of a herpes simplex virus (HSV) protein vaccine for protection against oral herpetic lesions and subsequent nervous tissue involvement. Oral HSV infections manifested either as primary gingivostomatitis or recurrent oral lesions (cold sores), have been recognized as a major dental problem for years. We propose to use the inbred BALB/c mouse strain in which oral herpetic lesions are regularly induced by swabbing abraded lip and buccal epithelial surfaces with a type 1 strain of HSV. A nucleic acid-free viral protein and/or glycoprotein vaccine preparation will be prepared and evaluated in this system. Antigen modification, using polymerized antigens and immunomodulators (pyran, poly IC) will be used in attempts to enhance the efficacy of the vaccines. Vaccine-mediated protection will be assessed by monitoring the degree of virus involvement in oral and nervous tissue, histopathology and ultrastructure of these tissues, and incidence of virus latency and recurrence. Vaccine efficacy will be correlated with various specific immunologic, humoral, and cellular proliferation and effector functions in immunized mice and matched non-immunized control animals.